Calcium flux into neurons and consequent production of phospholipid metabolites such as thromboxane A2 may cause permanent cellular injury after cerebral ischemia. Furthermore, the release of excitatory neurotransmitters such as glutamate may be the trigger causing opening of calcium channels. In this study, the effect on neuronal histology, electrophysiology, metabolism, learning ability, and CBF of nicardipine (Ni), a dihydropyridine calcium entry blocker, will be studied in male wistar rats rendered ischemic by 30 minutes of 4-vessel occlusion. Additional studies will evaluate Baclofen (Ba), an inhibitor of glutamate release, and 1 benzylimidazole (1-Bi), a thromboxane synthase inhibitor in combination with Ni. The hypothesis to be tested in this project is that Ni alone or augmented by Ba or 1-Bi will improve outcome following ischemia, and that this is associated with inhibition of calcium activated phospholipid metabolism. All animals will undergo vertebral artery cautery followed 24 hours later by carotid artery and collateral vessel occlusion for 30 minutes. Loss of righting reflex and EEG activity will be documented. Animals will be divided into 4 groups; normals, shams, untreated ischemic controls, and treatment with systemic Ni, Ba, 1-Bi, or combination therapy. Histologic damage in hippocampi, SEP amplitude and latency, and enzymatic quantitation of ATP, ATP turnover, and phosphocreatine in dissected hippocampal regions will be determined during 72 hours of reperfusion. Reference and working memory will be tested in an 8-arm radial maze over a 3 month period. Thromboxane B2 and 6-keto-PGF1a, indicators of phospholipid breakdown in this model, will be assayed during 72 hours of reperfusion. Finally, the effects of treatment on these measures of calcium activated neuronal dysruption will be compared to changes in regional cerebral blood flow measured by the 14C-butanol indicator fractionation technique.